Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction
Summary: Calorie restriction (CR) improves health and longevity. CR induces a periodic fasting cycle in mammals; our study compares CR with unanticipated fasting (F), when the food is unexpectedly withheld. F induces hepatic steatosis, whereas CR reduces it; surprisingly, the difference is not due t...
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472500912X |
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| author | Oghogho P. Ebeigbe Volha Mezhnina Artem Astafev Nikkhil Velingkaar Jillian Kodger Allan Poe Jonathan Fritz Kadaia Z. Williams Evelina Trokhimenko Josefa-Marie B. Rom Yana Sandlers Roman V. Kondratov |
| author_facet | Oghogho P. Ebeigbe Volha Mezhnina Artem Astafev Nikkhil Velingkaar Jillian Kodger Allan Poe Jonathan Fritz Kadaia Z. Williams Evelina Trokhimenko Josefa-Marie B. Rom Yana Sandlers Roman V. Kondratov |
| author_sort | Oghogho P. Ebeigbe |
| collection | DOAJ |
| description | Summary: Calorie restriction (CR) improves health and longevity. CR induces a periodic fasting cycle in mammals; our study compares CR with unanticipated fasting (F), when the food is unexpectedly withheld. F induces hepatic steatosis, whereas CR reduces it; surprisingly, the difference is not due to hepatic β-oxidation. Liver transcriptome analysis identifies fatty acid transporters (Slc27a1 and Slc27a2), triglyceride (TAG) synthesis (Gpat4), and lipid storage (Plin2 and Cidec) genes to be upregulated only in F, in agreement with hepatic steatosis. The circadian clock and anticipated fasting contribute to preventing fasting-associated hepatic steatosis in CR. Mechanistically, the Slc27a1, Plin2, and Cidec genes are upregulated, and liver TAGs accumulate in circadian clock mutant mice on CR or if wild-type CR mice miss their anticipated meal. The results highlight the similarities and differences between F and CR, suggesting that circadian clock–dependent gating of transcriptional response to fasting controls lipid homeostasis and prevents hepatic steatosis. |
| format | Article |
| id | doaj-art-b5af477208a34ab797e4a7f84e7335d0 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-b5af477208a34ab797e4a7f84e7335d02025-08-20T04:01:57ZengElsevierCell Reports2211-12472025-08-0144811614110.1016/j.celrep.2025.116141Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restrictionOghogho P. Ebeigbe0Volha Mezhnina1Artem Astafev2Nikkhil Velingkaar3Jillian Kodger4Allan Poe5Jonathan Fritz6Kadaia Z. Williams7Evelina Trokhimenko8Josefa-Marie B. Rom9Yana Sandlers10Roman V. Kondratov11Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USADepartment of Chemistry, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USADepartment of Chemistry, Cleveland State University, Cleveland, OH 44115, USACenter for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, OH 44115, USA; Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA; Corresponding authorSummary: Calorie restriction (CR) improves health and longevity. CR induces a periodic fasting cycle in mammals; our study compares CR with unanticipated fasting (F), when the food is unexpectedly withheld. F induces hepatic steatosis, whereas CR reduces it; surprisingly, the difference is not due to hepatic β-oxidation. Liver transcriptome analysis identifies fatty acid transporters (Slc27a1 and Slc27a2), triglyceride (TAG) synthesis (Gpat4), and lipid storage (Plin2 and Cidec) genes to be upregulated only in F, in agreement with hepatic steatosis. The circadian clock and anticipated fasting contribute to preventing fasting-associated hepatic steatosis in CR. Mechanistically, the Slc27a1, Plin2, and Cidec genes are upregulated, and liver TAGs accumulate in circadian clock mutant mice on CR or if wild-type CR mice miss their anticipated meal. The results highlight the similarities and differences between F and CR, suggesting that circadian clock–dependent gating of transcriptional response to fasting controls lipid homeostasis and prevents hepatic steatosis.http://www.sciencedirect.com/science/article/pii/S221112472500912XCP: Metabolism |
| spellingShingle | Oghogho P. Ebeigbe Volha Mezhnina Artem Astafev Nikkhil Velingkaar Jillian Kodger Allan Poe Jonathan Fritz Kadaia Z. Williams Evelina Trokhimenko Josefa-Marie B. Rom Yana Sandlers Roman V. Kondratov Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction Cell Reports CP: Metabolism |
| title | Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction |
| title_full | Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction |
| title_fullStr | Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction |
| title_full_unstemmed | Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction |
| title_short | Circadian clocks and periodic anticipated fasting prevent fasting-associated hepatic steatosis in calorie restriction |
| title_sort | circadian clocks and periodic anticipated fasting prevent fasting associated hepatic steatosis in calorie restriction |
| topic | CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S221112472500912X |
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